WO2000037106A1 - Oral vaccine against diarrhea - Google Patents
Oral vaccine against diarrhea Download PDFInfo
- Publication number
- WO2000037106A1 WO2000037106A1 PCT/SE1999/002306 SE9902306W WO0037106A1 WO 2000037106 A1 WO2000037106 A1 WO 2000037106A1 SE 9902306 W SE9902306 W SE 9902306W WO 0037106 A1 WO0037106 A1 WO 0037106A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cfa
- defined amount
- vaccine
- etec
- ctb
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/025—Enterobacteriales, e.g. Enterobacter
- A61K39/0258—Escherichia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55544—Bacterial toxins
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to an oral vaccine against diarrhea. More precisely, it relates to an oral vaccine composition against enterotoxigenic E.coli caused diarrhea in humans.
- CFA colonization factor antigens
- a number of bacteria which are of medical interest have been shown to produce CFAs associated with their membrane.
- the ones which are most important for humans are organisms which colonize the human gastrointestinal tract and the respiratory airways.
- organisms which colonize the gastrointestinal tract are enterotoxigenic Escherichia coli, Vibrio cholerae, Helicobacter pylori, Campylobacter, Shigellae, Salmonellae and Yersinia.
- ETEC enterotoxigenic Escherichia coli
- Enterotoxigenic E. coli are characterized in that they produce heat labile enterotoxin (LT) and/or heat stable enterotoxin (ST).
- LT heat labile enterotoxin
- ST heat stable enterotoxin
- CS-antigens heat stable enterotoxin
- the present invention provides a new vaccine composition which is based on LT- negative killed enterotoxigenic E. coli bacteria comprising defined amounts of at least three different types of colonization factor antigens, and the B-subunit of cholera toxin (CTB) which is antigenically similar to the heat labile enterotoxin of ETEC. Further, the vaccine composition is purified from possible heat stable enterotoxin (ST).
- ST heat stable enterotoxin
- the LT- negative ETEC bacteria are either laboratory selected from naturally genetically modified strains or produced by recombinant techniques.
- enterotoxin which is a comparatively small protein of 19 amino acid residues, is washed away during the down stream processing of the vaccine composition.
- the present invention provides an oral vaccine composition against enterotoxigenic E.coli caused diarrhea in humans, which comprises a defined amount of at least three different types of colonization factor antigens (CFAs) selected from the group consisting of CFA I, CFA II (CS 1, CS2 and CS3) and CFA IV (CS4, CS5 and CS6), on killed E.
- CFAs colonization factor antigens
- coli bacteria lacking the gene encoding the heat labile (LT " ) enterotoxin, together with a defined amount of the B-subunit of cholera toxin (CTB), and an vehicle, which vaccine composition is purified from possible heat stable enterotoxin (ST).
- LT heat labile enterotoxin
- the defined amount of different types of CFAs is for each type of CFA at least 100 ⁇ g, and the defined amount of CTB is at least 0.5 mg, and the vehicle is a physiologically acceptable buffer solution. In a preferred embodiment the defined amount of different types of CFAs is for each type of CFA 100 to 300 ⁇ g, and the defined amount of CTB is 0.5 to 2.0 mg.
- the defined amount of different types of CFAs are 200 ⁇ g of CFA/I, 200 ⁇ g of CSl, 150 ⁇ g of CS2, 200 ⁇ g of CS4 and 150 ⁇ g of CS5, and 1.0 mg of CTB, and the physiologically acceptable buffer solution is phosphate buffered saline solution.
- a dose of the vaccine composition will contain approximately 10 bacteria.
- the vaccine composition is administered to person as a drink in a glas of water containing carbonate buffer, such as sodium hydrogen carbonate.
- E. coli fimbriae antigens are detected by using an inhibition ELISA substantially as described by Lopez- Vidal Y., et al in the Journal of Clinical Microbiology, vol 26, 1967- 1972 (1988). Briefly, the bacterial sample to be analyzed is incubated together with a fixed amount of monoclonal antibody directed against the CFA. After incubation the mixture is transferred to a plate previously coated with CFA, where residual monoclonal antibody can bind to the CFA. Bound antibody is visualized by adding horseradish peroxidase conjugated anti-mouse immunoglobulin. As substrate, o-phenylenediaminedihydrochloride in a citrate buffer is used. The optical density is measured at 450 nm in a spectrophotometer connected to a computer equipped with a data reduction software. The optical density observed is inversely proportional to the concentration of antibody in the sample. Formulation of the vaccine composition
- strains SBL- 104 and SBL-105 also produced CS 6, but the amount thereof was not established.
- the strain SBL- 107 also produced CS3, but the amount thereof was not established.
- ETEC vaccine containing 1 mg of recombinant B-subunit of cholera toxin plus 10 11 formalin killed ETEC bacteria of five ETEC strains expressing the most common colonization factor antigens (CFA's) such as CFA I, CFA II (CS 1, CS2 and CS3) and CFA IN (CS4, CS5 and CS6); a B-subunit cholera whole cell vaccine (registered in Sweden since 1992), containing 1 mg recombinant subunit B cholera toxin and 10 u killed whole cells (Inaba, Ogawa, classical and El Tor); placebo containing 10 n killed E.coli K12.
- CFA's colonization factor antigens
- the formulations were suspended in 4 ml buffer and each dose of vaccine or placebo was given as a drink in 150 cc of a sodium hydrogen carbonate solution. Isolation and characterization of ETEC bacteria and the anti-CTB IgA ELISA were performed as described (Jertborn M., et al ibid).
- Reactogenicity results are as follows: In total 43 volunteers (17%) had mild to moderate gastrointestinal or general symptoms after the first, dose; 13 (16%) in the placebo, 13 (16%) in the cholera vaccine group and 17 (20%) in the ETEC vaccine group. After the second dose 20 (8%o) had symptoms; 6 (7%) in the placebo, 7 (9%) in the cholera vaccine group and 7 (8%) in the ETEC vaccine group. Statistically, there were no differences in the proportion of volunteers reporting symptoms between the study groups.
- ETEC diarrhea was defined as having three or more liquid stools, and ETEC, but no other pathogens, detected in pretreatment stools.
- ETEC ETEC
- Comparison of ETEC diarrhea rates was done by one-sided Fisher's exact test. All ETEC isolates in the Per Protocol population expressed colonization factors included in the vaccine.
- the cholera vaccine gave no detectable protection against ETEC as compared with the placebo group, but it is noteworthy that only two of the ETEC cases in the cholera vaccine group were caused by bacteria producing solely the heat-labile enterotoxin (LT) against which the cholera vaccine (through its B-subunit) can theoretically work.
- LT heat-labile enterotoxin
- the cholera vaccine is not supposed to have any effect.
Abstract
Description
Claims
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL14380899A IL143808A0 (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
BR9916278-4A BR9916278A (en) | 1998-12-18 | 1999-12-09 | Composition of oral vaccine against diarrhea and vaccine |
HU0104552A HUP0104552A3 (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
JP2000589216A JP2002532562A (en) | 1998-12-18 | 1999-12-09 | Oral vaccine for diarrhea |
EEP200100309A EE200100309A (en) | 1998-12-18 | 1999-12-09 | An oral vaccine composition against enterotoxigenic E. coli causing diarrhea |
EP99964847A EP1140159A1 (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
AU30889/00A AU778223B2 (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
MXPA01006200A MXPA01006200A (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea. |
PL348257A PL198438B1 (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
CA002352309A CA2352309A1 (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
KR1020017007484A KR20010101233A (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
HR20010433A HRP20010433A2 (en) | 1998-12-18 | 2001-06-08 | Oral vaccine against diarrhea |
NO20012889A NO20012889D0 (en) | 1998-12-18 | 2001-06-12 | Oral diarrhea vaccine ± |
IS5967A IS5967A (en) | 1998-12-18 | 2001-06-13 | Oral vaccine for diarrhea |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9804415-9 | 1998-12-18 | ||
SE9804415A SE515285C2 (en) | 1998-12-18 | 1998-12-18 | Oral vaccine for diarrhea |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000037106A1 true WO2000037106A1 (en) | 2000-06-29 |
Family
ID=20413742
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1999/002306 WO2000037106A1 (en) | 1998-12-18 | 1999-12-09 | Oral vaccine against diarrhea |
Country Status (25)
Country | Link |
---|---|
EP (2) | EP1444987A3 (en) |
JP (1) | JP2002532562A (en) |
KR (1) | KR20010101233A (en) |
CN (1) | CN1330552A (en) |
AP (1) | AP1426A (en) |
AU (1) | AU778223B2 (en) |
BR (1) | BR9916278A (en) |
CA (1) | CA2352309A1 (en) |
CZ (1) | CZ20011947A3 (en) |
EE (1) | EE200100309A (en) |
HR (1) | HRP20010433A2 (en) |
HU (1) | HUP0104552A3 (en) |
ID (1) | ID29857A (en) |
IL (1) | IL143808A0 (en) |
IS (1) | IS5967A (en) |
MX (1) | MXPA01006200A (en) |
NO (1) | NO20012889D0 (en) |
NZ (1) | NZ527559A (en) |
OA (1) | OA11729A (en) |
PL (1) | PL198438B1 (en) |
SE (1) | SE515285C2 (en) |
TR (1) | TR200101542T2 (en) |
WO (1) | WO2000037106A1 (en) |
YU (1) | YU41701A (en) |
ZA (1) | ZA200104362B (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003022306A2 (en) * | 2001-09-11 | 2003-03-20 | Acambis Research Limited | Bacterial vaccine |
EP1543836A1 (en) * | 2003-12-17 | 2005-06-22 | Berna Biotech AG | Recombinant Vibrio cholerae strain and vaccine comprising said strain |
US7527802B2 (en) * | 2001-02-13 | 2009-05-05 | The United States Of America As Represented By The Secretary Of The Army | Vaccine for transcutaneous immunization |
US10414806B2 (en) * | 2011-09-12 | 2019-09-17 | Scandinavian Biopharma Holding Ab | Method for increasing ETEC CS6 antigen presentation on cell surface and products obtainable thereof |
US11052143B2 (en) * | 2011-09-12 | 2021-07-06 | Scandinavian Biopharma Holding Ab | Vaccine for protection against ETEC-induced diarrhea comprising dmLT |
RU2753410C2 (en) * | 2020-01-14 | 2021-08-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный аграрный университет имени И.Т. Трубилина" | Method for obtaining toxoid vaccine against escherichiosis of animals |
RU2813771C1 (en) * | 2022-11-17 | 2024-02-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный аграрный университет имени И.Т. Трубилина" | Method of preventing escherichiosis in calves |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8287855B2 (en) * | 2007-04-24 | 2012-10-16 | Celldex Therapeutics, Inc. | V. cholerae hyperexpressing recombinant cholera toxin B subunit showing dual immunogenicity |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992014487A1 (en) * | 1991-02-26 | 1992-09-03 | Jan Holmgren | Preparation and use of formalin-killed colonization-factor-antigen (cfa)-expressing e. coli organisms for vaccination against enteric infection/diarrhea caused by enterotoxigenic e. coli bacteria in humans |
-
1998
- 1998-12-18 SE SE9804415A patent/SE515285C2/en not_active IP Right Cessation
-
1999
- 1999-12-09 PL PL348257A patent/PL198438B1/en unknown
- 1999-12-09 JP JP2000589216A patent/JP2002532562A/en not_active Withdrawn
- 1999-12-09 CN CN99814553A patent/CN1330552A/en active Pending
- 1999-12-09 AP APAP/P/2001/002174A patent/AP1426A/en active
- 1999-12-09 KR KR1020017007484A patent/KR20010101233A/en not_active Application Discontinuation
- 1999-12-09 EE EEP200100309A patent/EE200100309A/en unknown
- 1999-12-09 HU HU0104552A patent/HUP0104552A3/en unknown
- 1999-12-09 ID IDW00200101304A patent/ID29857A/en unknown
- 1999-12-09 BR BR9916278-4A patent/BR9916278A/en not_active Application Discontinuation
- 1999-12-09 EP EP04010662A patent/EP1444987A3/en not_active Withdrawn
- 1999-12-09 OA OA1200100151A patent/OA11729A/en unknown
- 1999-12-09 EP EP99964847A patent/EP1140159A1/en not_active Withdrawn
- 1999-12-09 TR TR2001/01542T patent/TR200101542T2/en unknown
- 1999-12-09 NZ NZ527559A patent/NZ527559A/en unknown
- 1999-12-09 CA CA002352309A patent/CA2352309A1/en not_active Abandoned
- 1999-12-09 CZ CZ20011947A patent/CZ20011947A3/en unknown
- 1999-12-09 AU AU30889/00A patent/AU778223B2/en not_active Ceased
- 1999-12-09 IL IL14380899A patent/IL143808A0/en not_active IP Right Cessation
- 1999-12-09 MX MXPA01006200A patent/MXPA01006200A/en not_active IP Right Cessation
- 1999-12-09 YU YU41701A patent/YU41701A/en unknown
- 1999-12-09 WO PCT/SE1999/002306 patent/WO2000037106A1/en not_active Application Discontinuation
-
2001
- 2001-05-28 ZA ZA200104362A patent/ZA200104362B/en unknown
- 2001-06-08 HR HR20010433A patent/HRP20010433A2/en not_active Application Discontinuation
- 2001-06-12 NO NO20012889A patent/NO20012889D0/en not_active Application Discontinuation
- 2001-06-13 IS IS5967A patent/IS5967A/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992014487A1 (en) * | 1991-02-26 | 1992-09-03 | Jan Holmgren | Preparation and use of formalin-killed colonization-factor-antigen (cfa)-expressing e. coli organisms for vaccination against enteric infection/diarrhea caused by enterotoxigenic e. coli bacteria in humans |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7527802B2 (en) * | 2001-02-13 | 2009-05-05 | The United States Of America As Represented By The Secretary Of The Army | Vaccine for transcutaneous immunization |
US7951361B2 (en) | 2001-09-11 | 2011-05-31 | Acambis Research Limited | Bacterial vaccine |
WO2003022306A3 (en) * | 2001-09-11 | 2003-06-26 | Acambis Res Ltd | Bacterial vaccine |
US8318148B2 (en) | 2001-09-11 | 2012-11-27 | Acambis Research Limited | Attenuated bacteria useful in vaccines |
WO2003022306A2 (en) * | 2001-09-11 | 2003-03-20 | Acambis Research Limited | Bacterial vaccine |
US7943122B2 (en) | 2001-09-11 | 2011-05-17 | Acambis Research Limited | Attenuated bacteria useful in vaccines |
WO2005058354A1 (en) * | 2003-12-17 | 2005-06-30 | Berna Biotech Ag | Recombinant vibrio cholerae strain and vaccine comprising said strain |
EP1543836A1 (en) * | 2003-12-17 | 2005-06-22 | Berna Biotech AG | Recombinant Vibrio cholerae strain and vaccine comprising said strain |
US10414806B2 (en) * | 2011-09-12 | 2019-09-17 | Scandinavian Biopharma Holding Ab | Method for increasing ETEC CS6 antigen presentation on cell surface and products obtainable thereof |
US10851140B2 (en) | 2011-09-12 | 2020-12-01 | Scandinavian Biopharma Holding Ab | Method for increasing ETEC CS6 antigen presentation on cell surface and products obtainable thereof |
US11052143B2 (en) * | 2011-09-12 | 2021-07-06 | Scandinavian Biopharma Holding Ab | Vaccine for protection against ETEC-induced diarrhea comprising dmLT |
US11820798B2 (en) | 2011-09-12 | 2023-11-21 | Scandinavian Biopharma Holding Ab | Method for increasing ETEC CS6 antigen presentation on cell surface and products obtainable thereof |
US11918636B2 (en) * | 2011-09-12 | 2024-03-05 | SCANDINAVIAN BIOPHARMA HOLDING AB, c/o Etvax AB | Vaccine for protection against ETEC-induced diarrhea comprising dmLT |
RU2753410C2 (en) * | 2020-01-14 | 2021-08-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный аграрный университет имени И.Т. Трубилина" | Method for obtaining toxoid vaccine against escherichiosis of animals |
RU2813771C1 (en) * | 2022-11-17 | 2024-02-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный аграрный университет имени И.Т. Трубилина" | Method of preventing escherichiosis in calves |
Also Published As
Publication number | Publication date |
---|---|
HRP20010433A2 (en) | 2002-06-30 |
EP1444987A2 (en) | 2004-08-11 |
OA11729A (en) | 2005-05-12 |
BR9916278A (en) | 2001-09-04 |
JP2002532562A (en) | 2002-10-02 |
CN1330552A (en) | 2002-01-09 |
EE200100309A (en) | 2002-08-15 |
AU778223B2 (en) | 2004-11-25 |
NO20012889L (en) | 2001-06-12 |
EP1140159A1 (en) | 2001-10-10 |
SE515285C2 (en) | 2001-07-09 |
ID29857A (en) | 2001-10-18 |
NZ527559A (en) | 2005-01-28 |
HUP0104552A2 (en) | 2002-04-29 |
AU3088900A (en) | 2000-07-12 |
CZ20011947A3 (en) | 2001-12-12 |
IS5967A (en) | 2001-06-13 |
EP1444987A3 (en) | 2005-12-21 |
ZA200104362B (en) | 2002-01-14 |
HUP0104552A3 (en) | 2002-08-28 |
SE9804415L (en) | 2000-06-19 |
MXPA01006200A (en) | 2002-04-17 |
AP1426A (en) | 2005-06-06 |
PL198438B1 (en) | 2008-06-30 |
SE9804415D0 (en) | 1998-12-18 |
KR20010101233A (en) | 2001-11-14 |
YU41701A (en) | 2005-07-19 |
IL143808A0 (en) | 2002-04-21 |
CA2352309A1 (en) | 2000-06-29 |
TR200101542T2 (en) | 2001-10-22 |
NO20012889D0 (en) | 2001-06-12 |
PL348257A1 (en) | 2002-05-20 |
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